Effects of Ganoderma lucidum on rheumatoid synovial fibroblasts
Effects of Ganoderma Lucidum on Rheumatoid Synovial Fibroblasts
submitted by EVA YEEWAHO
for the Degree of Master of Philosophy at the University of Hong Kong
in December 2003
Rheumatoid arthritis (RA) is a prototypical chronic inflammatory disease manifested by progressive synovial joint inflammation and erosion of the subchondral bone. The severity of the joint inflammation fluctuates over time, and the outcome in uncontrolled disease is progressive joint destruction, deformity, and disability. Efficacy of currently used antirheumatic therapy is often limited and frequent problems are side effects, either cumulative or idiosyncratic, and high cost. Abnormal proliferation of synovial fibroblasts and excessive secretion of pro-inflammatory cytokines such as interleukin (IL )-6, IL-8 and monocyte chemoattractant protein (MCP)-l are the main destructive effects of synovial fibroblasts in RA joint.
Ganoderma /ucidum (Leyss, Ex Fr.), is a medicinal mushroom. G. /ucidum polysaccharides, one of the main effective components of G. /ucidum, have been reported to be effective in modulating immune functions. The reactions of different
types of cells in the immune system to G. /ucidum were not the same (Zhu & Mori 1994). This may explain the reason that G. /ucidum has been used in various human diseases such as hepatitis, hypertension, arthritis, bronchitis and tumorigenic diseases in oriental folk medicine (Seong et a1 1999).
Many RA patients have claimed G. /ucidum can to some extent alleviate the symptoms of their arthritis condition. In addition, G. /ucidum has been shown to have immuno-modu1atory, anti-inflammatory and analgesic effects in preclinical studies (Wasser and Weis 1999; Giner-Larza et a1 2001). G. /ucidum has been shown to modulate production of several cytokines, such as tumor necrosis factor (TNF)-a and ILs such as IL-1~, IL-2 and IL-6, which are all associated with the pathogenesis of RA (Ye et a1 2001). Up to my knowledge, there has been no research of G. /ucidum on RA synovial fibroblast. Therefore, I would like to find out the scientific evidence to support the potential use of G. /ucidum in RA therapy. The aim of this project is to elucidate the effects of G. /ucidum polysaccharides on RA synovial fibroblasts.
Synovial tissues were obtained from patients with RA at the time of surgery; isolated synovial fibroblasts were used at passage of 6 or over. Preliminary experiments have shown that G. /ucidum had significant inhibitory effect on the proliferation of RA synovial fibroblast. G. /ucidum did not have any stimulatory effects on RA synovial fibroblasts in the production of IL-10, IL-1 ~ and TNF -a. On the other hand, G. /ucidum had slight stimulatory effects on the basal production of IL-6 and MCP-1. However, the actual stimulatory effects were minimal due to the low basal values. ILl ~ and LPS were used to mimic the actual environment in active RA joints. Results showed that G. /ucidum significantly suppressed either IL-1 ~ or LPS induced IL-8
and MCP-l production. The inhibitory effects of G. /ucidum on RA synovial fibroblast are at least in part, by inhibiting NF-KB transcription pathway. More experiments are required for further investigation on the potential use of G. /ucidum in RA therapy. This pilot study demonstrated that G. /ucidum is a non-toxic medicine and has immunomodulatory effects on cytokine production by RA synovial fibroblast.
School:The University of Hong Kong
School Location:China - Hong Kong SAR
Source Type:Master's Thesis
Keywords:ganoderma lucidum therapeutic use synovial membranes effect of drugs on fibroblasts rheumatoid arthritis
Date of Publication:01/01/2004